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Article Dans Une Revue Acta Neuropathologica Année : 2021

Oligosarcomas, idh-mutant are distinct and aggressive

Abigail K. Suwala
  • Fonction : Auteur
Dennis Friedel
  • Fonction : Auteur
Damian Stichel
  • Fonction : Auteur
Daniel Schrimpf
  • Fonction : Auteur
Felix Hinz
  • Fonction : Auteur
Ekkehard Hewer
  • Fonction : Auteur
Leonille Schweizer
  • Fonction : Auteur
Hildegard Dohmen
  • Fonction : Auteur
Ute Pohl
  • Fonction : Auteur
Marco Stein
  • Fonction : Auteur
Thidathip Wongsurawat
  • Fonction : Auteur
Pornsuk Cheunsuacchon
  • Fonction : Auteur
Sith Sathornsumetee
  • Fonction : Auteur
Clinton Turner
  • Fonction : Auteur
Angelika Muhlebner
  • Fonction : Auteur
Koray Ozduman
  • Fonction : Auteur
Takahiro Ono
  • Fonction : Auteur
Hiroaki Shimizu
  • Fonction : Auteur
Marco Prinz
  • Fonction : Auteur
Till Acker
  • Fonction : Auteur
Christel Herold-Mende
  • Fonction : Auteur
Tobias Kessler
  • Fonction : Auteur
Wolfgang Wick
  • Fonction : Auteur
David Capper
  • Fonction : Auteur
Pieter Wesseling
  • Fonction : Auteur
Felix Sahm
  • Fonction : Auteur
Andreas von Deimling
  • Fonction : Auteur
Christian Hartmann
  • Fonction : Auteur

Résumé

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.
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hal-04019239 , version 1 (08-03-2023)

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Abigail K. Suwala, Marius Felix, Dennis Friedel, Damian Stichel, Daniel Schrimpf, et al.. Oligosarcomas, idh-mutant are distinct and aggressive. Acta Neuropathologica, 2021, 143, pp.263-281. ⟨10.1007/s00401-021-02395-z⟩. ⟨hal-04019239⟩

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